Cell adhesion inhibitors

Abstract

The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.

We claim:  
     
       1. A cell adhesion inhibitory compound selected from a compound of the formula (I):                    
       and pharmaceutically acceptable derivatives of (I), wherein: 
       X is selected from the group consisting of —CO 2 H, —PO −   3 H, —SO 2 R 5 , —SO 3 H, —OPO −   3 H, and —CO 2 R 4 ; wherein R 5  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aryl-substituted alkyl, and aryl-substituted alkenyl or alkynyl;  
       Y is selected from the group consisting of —CO—, —SO 2 — and —PO 2 —;  
       R 1  is selected from the group consisting of alkenyl, alkynyl, cycloalkyl, aryl-fused cycloalkyl, cycloalkenyl, aryl, substituted aralkyl, aryl-substituted alkenyl or alkynyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, biaryl, alkenyloxy, alkyloxy, aryloxy, aryl-substituted alkenyloxy or alkyloxy, alkylamino, alkenylamino or alkynylamino, aryl-substituted alkylamino, aryl-substituted alkenylamino or alkynylamino, aryloxy, arylamino, N-alkylurea-substituted C 1 -C 4  alkyl, N-arylurea-substituted C 1 -C 4  alkyl, aminocarbonyl-substituted alkyl, heterocyclyl, heterocyclyl-substituted alkyl, heterocycly-substituted amino, carboxylalkyl substituted aralkyl, oxocarbocyclyl-fused aryl and heterocyclylalkyl;  
       R 2  is selected from the group consisting of hydrogen, aryl, alkyl alkenyl or alkynyl, cycloalkyl, cycloalkenyl, aryl-substituted alkyl and, wherein R 2  and R 3  may be taken together with the atoms to which they are attached, to form a heterocycle;  
       R 3  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl-substituted alkenyl or alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl-substituted alkenyl or alkynyl, hydroxy-substituted alkyl, alkoxy-substituted alkyl, arylkoxy-substituted alkyl, amino-substituted alkyl, (aryl-substituted alkyloxycarbonylamino)-substituted alkyl, thiol-substituted alkyl, alkylsulfonyl-substituted alkyl, (hydroxy-substituted alkylthio)-substituted alkyl, thioalkoxy-substituted alkyl, acylamino-substituted alkyl, alkylsulfonylamino-substituted alkyl, arylsulfonylamino-substituted alkyl, morpholino-alkyl, thiomorpholino-alkyl, morpholino carbonyl-substituted alkyl, thiomorpholinocarbonyl-substituted alkyl, (N-alkyl, alkenyl or alkynyl)- or N,N-(dialkyl, dialkenyl, dialkynyl)- or N,N-(alkyl,alkenyl)-aminocarbonyl-substituted alkyl, carboxyl-substituted alkyl, dialkylamino-substituted acylaminoalkyl and amino acid side chains selected from arginine, asparagine, glutamine, S-methyl cysteine, methionine and corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, norleucine, phenylalanine, tyrosine, tryptophan, proline, alanine, ornithine, histidine, glutamine, valine, threonine, serine, betacyanoalanine, and allothreonine; and wherein R 2  and R 3  may be taken together with the atoms to which they are attached, to form a heterocycle;  
       R 4  is selected from the group consisting of aryl, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl and aryl-substituted alkyl, hydrogen, heterocyclyl, heterocyclylcarbonyl, amido, mono- or dialkylaminocarbonyl, mono- or diarylaminocarbonyl, alkylarylaminocarbonyl, diarylaminocarbonyl, mono- or diacylaminocarbonyl, aromatic acyl, alkyl optionally substituted by stubstituents selected from the group consisting of amino, carboxy, hydroxy, mercapto, mono- or dialkylamino, mono- or diarylamino, alkylarylamino, diarylamino, mono- or diacylamino, alkoxy, alkenyloxy, aryloxy, thioalkoxy, thioalkenoxy, thioalkynoxy, thioaryloxy and heterocyclyl; and  
       n is 0, 1, or 2; and  
       at least one of R 1 -R 5  includes a heterocyclic group.  
     
     
       2. The compound according to  claim 1  selected from a compound of the formula (I):                    
       and pharmaceutically acceptable derivatives of (I), wherein: 
       X is selected from the group consisting of —CO 2 H, —PO −   3 H, —SO 2 R 5 , —SO 3 H, and —OPO −   3 H; wherein R 5  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aryl-substituted alkyl, and aryl-substituted alkenyl or alkynyl;  
       Y is selected from the group consisting of —CO—, —SO 2 — and —PO 2 —;  
       R 1  is selected from the group consisting of alkenyl, alkynyl, cycloalkyl, aryl-fused cycloalkyl, cycloalkenyl, aryl, substituted aryl-substituted alkyl (“aralkyl”), aryl-substituted alkenyl or alkynyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted cycloalkyl, biaryl, alkenyloxy, alkyloxy, aryl-substituted alkoxy (“aryloxy”), aryl-substituted alkenyloxy or alkyloxy, alkylamino, alkenylamino or alkynylamino, aryl-substituted alkylamino, aryl-substituted alkenylamino or alkynylamino, aryloxy, arylamino, N-alkylurea-substituted C 1 -C 4  alkyl, N-arylurea-substituted C 1 -C 4  alkyl, and aminocarbonyl-substituted alkyl;  
       R 2  is selected from the group consisting of hydrogen, aryl, alkyl, alkenyl or alkynyl, cycloalkyl, cycloalkenyl, and aryl-substituted alkyl;  
       R 3  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl-substituted alkenyl or alkynyl, hydroxy-substituted alkyl, alkoxy-substituted alkyl, aryloxy-substituted alkyl, amino-substituted alkyl, (aryl-substituted alkyloxycarbonylamino)-substituted alkyl, thiol-substituted alkyl, alkylsulfonyl-substituted alkyl, (hydroxy-substituted alkylthio)-substituted alkyl, thioalkoxy-substituted alkyl, acylamino-substituted alkyl, alkylsulfonylamino-substituted alkyl, arylsulfonylamino-substituted alkyl, morpholino-alkyl, thiomorpholino-alkyl, morpholino carbonyl-substituted alkyl, thiomorpholinocarbonyl-substituted alkyl, N-(alkyl, alkenyl or alkynyl)- or N,N-(dialkyl, dialkenyl, dialkynyl)- or N,N-(alkyl, alkenyl)-aminocarbonyl-substituted alkyl, carboxyl-substituted alkyl, and amino acid side chains selected from arginine, asparagine, glutamine, S-methyl cysteine, methionine and corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, norleucine, phenylalanine, tyrosine, tryptophan, proline, alanine, ornithine, histidine, glutamine, valine, threonine, serine, beta-cyanoalanine, and allothreonine;  
       R 4  is selected from the group consisting of aryl, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl and aryl-substituted alkyl;  
       n is 0, 1, or 2; and  
       at least one of R 1 -R 5  includes a heterocyclic group.  
     
     
       3. The cell adhesion inhibitory compound according to  claim 1 , wherein X is —CO 2 H. 
     
     
       4. The cell adhesion inhibitory compound according to  claim 1 , wherein R 1  is an aryl-substituted C 1 -C 4  alkyl group. 
     
     
       5. The cell adhesion inhibitory compound according to  claim 4 , wherein R 1  is (N′-Ar-urea) wherein the urea is substituted at the para position of the arylalkyl. 
     
     
       6. The cell adhesion inhibitory compound according to  claim 5 , wherein R 1  is (N 1 -Ar-urea wherein the urea is substituted at the para position of the phenylmethyl. 
     
     
       7. The cell adhesion inhibitory compound according to  claim 1 , wherein R 1 , is selected from the group consisting of cyanomethyl, cyclohexylmethyl, N-phenylamino, phenyl, phenylcarbonyl, phenylmethyl, t-butylamino, 1-indanyl, 1-naphthylmethyl, 1-phenylcyclopropyl, 2-(4-hydroxy-phenyl)ethyl, 2-(benzyloxycarbonylamino) phenylmethyl, 2-(bis(phenylsulfonyl)amino)-phenylmethyl, 2-(N′-phenylurea)phenylmethyl, 2-aminophenylmethyl, 2-benzamidophenylmethyl, 2-bromo-4-hydroxy-5-methoxyphenylmethyl, 2-hydroxyphenylmethyl, 2naphthylmethyl, 2-phenylethyl, 2-pyridylmethyl, 2quinolinyl,2-[4-(N′-phenylurea)phenyl]-ethyl, 3-(benzyloxycarbonylamino)-phenylmethyl, 2-(N′-phenylurea)phenylmethyl, 2-(N′-phenylurea)propyl, 3(phenylsulfonamido)-phenylmethyl, 3-acetamidophenylmethyl, 3-aminophenylmethyl, 3-benzamidophenylmethyl, 3-hydroxy-4-(N′-phenylurea)-phenylmethyl, 3-hydroxyphenylmethyl, 3-indolyl, 3-methoxy-4-(N′-phenylurea)-phenylmethyl, 3-methoxy-4-(N′-(2-methylphenyl)-urea)phenylmethyl, 3-methyl-4-(N′-phenylurea)-phenylmethyl, 3-nitrophenylmethyl, 3-phenylpropyl, 3-pyridylmethyl,4-(2-aminobenzamido)-phenylmethyl, 4-(benzamido)phenyl-methyl, 4-(benzyloxycarbonylamino)-phenylmethyl, 4-(morpholinocarbonyl-amino)-phenylmethyl, 4-(N′-(2-chlorophenyl)urea)-phenylmethyl, 4-(N′-(2-chlorophenyl) urea)-3-methoxyphenylmethyl, 4-(N′-(2-ethylphenyl) urea)phenylmethyl, 4-(N′-(2-isopropylphenyl)urea) phenylmethyl, 4-(N′-(2-methoxyphenylurea)-phenyl-methyl, 4-(N′-(2-methyl-3-pyridyl)urea)-phenylmethyl, 4-(N′-(2-nitrophenyl)urea)-phenylmethyl, 4-(N′-(2-pyridyl)urea)phenylmethyl, 4-(N′-(2-t-butylphenyl)-urea)-phenylmethyl, 4-(N′-(2-thiazolyl)urea)-phenyl-methyl, 4-(N′-(3-chlorophenyl)urea)-phenylmethyl, 4-(N′-(3-methoxyphenyl)urea)-phenylmethyl, 4-(N′-(3-pyridyl)urea)phenylmethyl, 4-(N′-(4-pyridyl)urea)-phenylmethyl, 4-(N′-(3-methylphenyl)urea)-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4-(N′-benzylurea)phenylmethyl, 4-(N′-cyclohexylurea)-phenylmethyl, 4-(N′-ethylurea)phenylmethyl, 4-(N′-isopropylurea)-phenylmethyl, 4-(N′-methylurea)-phenylmethyl, 4-(N′-p-toluylurea)phenylmethyl, 4-(N′-phenylurea)phenyl, 4-(N′phenylurea)phenylamino, 4-(N′-phenylurea)phenyl-methyl, 4(N′-t-butylurea)-phenylmethyl, 4-(phenylaminocarbonyl amino-methyl)-phenyl, 4-(phenylsulfonamido)phenylmethyl, 4-(t-butoxycarbonyl-amino)-phenylmethyl, 4-acetamidophenylmethyl, 4-aminophenylamino, 4-aminophenylmethyl, 4-benzamidophenylmethyl, 4-chlorophenylmethyl, 4-hydroxy-3-nitrophenylmethyl, 4-hydroxyphenylmethyl, 4-methoxyphenylmethyl, 4-nitrophenylamino, 4-nitrophenylmethyl, 4-phenacetamidophenylmethyl, 4phenylphenylmethyl, 4-pyridylmethyl, 4-trifluoromethylphenylmethyl, 4-[2-(N′-methylurea)-benzamido]-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4(N′-phenyl-N′-methylguanidino)-phenylmethyl, 5-(N′phenylurea)pentyl, 5-(N′-t-butylurea)pentyl, 2,2-dimethylpropyl, 2,2-diphenylmethyl, 2,3-benzocyclobutyl, 3,4-dihydroxyphenylmethyl, 3,5-dimethoxy-4-hydroxyphenylmethyl, 4-(1-indolecarboxylamino)-phenylmethyl, 6-methoxy-5-(N′-(2-methylphenyl)urea)-2-pyridylmethyl, 4(1,3-benzoxazol-2-ylamino)-phenylmethyl, 4-(1,3imidazol-2-ylamino)-phenylmethyl, 3-carboxy-1-phenylpropyl; 3-hydroxy-4-(2-methylphenyl)ureaphenylmethyl; 3-hydroxy-4-(2-chlorophenyl)ureaphenylmethyl; 6-(phenylurea)heptyl, 4-phenylurea)butyl; 2-thienylmethyl; 4-(2,6-dimethylphenylurea)phenylmethyl; 4-(2-hydroxyphenylurea)phenylmethyl; 3-butoxy-4-(2-methylphenyl)ureaphenylmethyl; 3-butoxy-4-(phenylurea)phenylmethyl; 4-(N-2-pyrazinylurea)phenylmethyl; 2-phenylethynyl; 5-phenylurea-2-pyridylmethyl; 5-(2-methylphenylurea)-2-pyridylmethyl; 4-(3-methyl-2-pyridylurea)phenylmethyl; 3-nitro-4(phenylurea)phenylmethyl; 3-acylamino-4-(phenylurea)phenylmethyl; 4-(N,N-phenyl, methylurea)phenylmethyl; 4-(3-hydroxyphenylurea)phenylmethyl; 4-(2-acetylaminophenylurea)phenylmethyl; 4-(2-propionylaminophenylurea)phenylmethyl; 4-(3-benzyloxy-2-pyridylurea)phenylmethyl; 4-(3-methyl-2-pyridylurea)phenylmethyl; 4-(indolylcarbonylamino)phenylmethyl; 2-(4-(phenylurea)phenyl)oxiranyl; 4-(N,N′-phenyl, methylurea)phenylmethyl; 4-(2-dimethylaminophenylurea)phenylmethyl; 4-(-benzimidazolylamino)phenylmethyl; 4-(2-benzoxazolylamino)phenylmethyl; 4-(2-benzthiazolylamino)phenylmethyl; 4-(tetrahydroquinolinylcarbonylamino)phenylmethyl; 1,3-dimethyl-3-(phenylurea)butyl; hydroxyethylthiomethyl; 4-(phenylurea)phenylethenyl; 3-amino-4-(phenylurea)phenylmethyl; 4-(4-hydroxyphenylurea)phenylmethyl; 4-(2-aminophenylurea)phenylmethyl; 4-((2-methylurea)phenylurea)phenyl; 4-(2-hydroxyphenylurea)-3-methoxyphenylmethyl; 4-(2-methylsulfonylmethylphenylurea)phenylmethyl; 4-(2-methylphenylurea)tetrahydro-2-pyrimidonylmethyl; 3-methoxy-4-(phenylurea)-2-pyridyhnethyl; 4-(2-trifluoromethylphenylurea)phenylmethyl; 4-(3-methyl-2-pyridylurea)phenylmethyl; 4-(2,4-(1H,3H)-quinazolinedionyl)phenylmethyl; 4-thioureaphenylmethyl; 4-(phenylthiourea)phenylmethyl; 4-(pyrrolidinylcarbonylamino)phenylmethyl; 4-(2-benzoxazolinonylcarbonylamino)phenylmethyl; 4-(benzyloxyurea)phenylmethyl; 4-(thiazolidinylcarbonylamino)phenylmethyl; 4-benzoylureaphenylmethyl; hydroxylureaphenylmethyl; N″N″methyl, hydroxylureaphenylmethyl; 4-(N′-allylurea)phenylmethyl; 4-(3-pyrrolidinylcarbonylamino)phenylmethyl; 4-(1-pyrrolylcarbonylamino)phenylmethyl; 4-(2-pyrrolylcarbonylamino)phenylmethyl; 4-(propylurea)phenylmethyl; 4-(methoxyurea)phenylmethyl; 4-(dimethylurea)phenylmethyl; 4-(2-quinazolinylamino)phenylmethyl; 4-(2-furanoylamino)phenylmethyl; 4-(2-hydroxy-6-methylphenylurea)phenylmethyl; 4-(2-pyridylcarbonylamino)phenylmethyl; 4-(3-hydroxy-2-methylphenylurea)phenylmethyl; 4-(2-fluorophenylurea)phenylmethyl; 4-(3-fluorophenylurea)phenylmethyl; 4-(4-fluorophenylurea)phenylmethyl; 4-(2-quinolinylcarbonylamino)phenylmethyl; 4-(isoquinolinylcarbonylamino)phenylmethyl; 4-(2,3-dimethylphenylurea)phenylmethyl; 4-(2,5-dimethylphenylurea)phenylmethyl; 4-(2-methyl-4-fluorophenylurea)phenylmethyl; 4-(2-methyl-3-fluorophenylurea)phenylmethyl; 3-carboxy-3-phenylpropyl; 4-(5-hydroxy-2-methylphenylurea)phenylmethyl; 4-(4-hydroxy-2-methylphenylurea)phenylmethyl; 4-(2,4-difluorophenylurea)phenylmethyl; 3-dibenzofuranylcarbonyl; 4-(phenoxycarbonylamino)phenylmethyl; 3-phenylureapropyl; 4-(phenylaminocarbonyloxy)phenylmethyl; 4-cinnamoylphenylmethyl; dibenzofuranylmethyl; 4-(2-methylphenylaminocarbonloxy)phenylmethyl; methylphenylurea)phenylamino; 4-(3-indolylcarbonylamino)phenylmethyl; 4-(phenylaminocarbonyl)phenylmethyl; 4-phenylalkynylphenylmethyl; 4-(3-pyrrolylcarbonylamino)phenylmethyl; 5-nitrobenzofuran-2-yl; 5-(2 methylphenylurea)benzofuran-2-yl; 3-carboxy-3-phenylpropyl; 2-(3-pyridyl)-thiazol-4-yl; 2-(4-pyridyl)-thiazol-4-yl; 2-oxo- and 4-oxo4,5,6,7-tetrahydrobenzo[b]furan-3-yl; 3-methoxy-4-(phenylcarbamoyloxy)phenylmethyl; 5-amino-benzofuran-2-yl; benzilylaminophenylmethyl and 4-[N-2-carboxyethyl-1-(1,3-benzodioxolyl-5-yl)amino-N-leucinylacetamidylphenylurea]-phenylmethyl. 
     
     
       8. The cell adhesion inhibitory compound according to  claim 1 , wherein R 1  is selected from the group consisting of cyanomethyl, cyclohexylmethyl, N-phenylamino, phenyl, phenylcarbonyl, phenylmethyl, t-butylamino, 1-indanyl, 1-naphthylmethyl, 1-phenylcyclopropyl, 2-(4-hydroxy-phenyl)ethyl, 2-(benzyloxycarbonylamino)phenylmethyl, 2-(bis(phenylsulfonyl)amino)-phenylmethyl, 2-(N′-phenylurea)phenylmethyl, 2-aminophenylmethyl, 2-benzamidophenylmethyl, 2-bromo-4-hydroxy-5-methoxyphenylmethyl, 2-hydroxyphenylmethyl, 2naphthylmethyl, 2-phenylethyl, 2-pyridylmethyl, 2quinolinyl,2-[4-(N′-phenylurea)phenyl]-ethyl, 3-(benzyloxycarbonylamino)-phenylmethyl, 3-(N′-phenylurea)phenylmethyl, 3-(N′-phenylurea)propyl, 3(phenylsulfonamido)-phenylmethyl, 3-acetamidophenylmethyl, 3-aminophenylmethyl, 3-benzamidophenylmethyl, 3-hydroxy-4-(N′-phenylurea)-phenylmethyl, 3-hydroxyphenylmethyl, 3-indolyl, 3-methoxy-4-(N′-phenylurea)-phenylmethyl, 3-methoxy-4-(N′-(2-methylphenyl)-urea)phenylmethyl, 3-methyl-4-(N′-phenylurea)-phenylmethyl, 3-nitrophenylmethyl, 3-phenylpropyl, 3-pyridylmethyl, 4-(2-aminobenzamido)-phenylmethyl, 4-(benzamido)phenyl-methyl, 4-(benzyloxycarbonylamino)-phenylmethyl, 4-(morpholinocarbonyl-amino)-phenylmethyl, 4-(N′-(2-chlorophenyl)urea)-phenylmethyl, 4-(N′-(2-chlorophenyl) urea)-3-methoxyphenylmethyl, 4-(N′-(2-ethylphenyl) urea)phenylmethyl, 4-(N′-(2-isopropylphenyl)urea) phenylmethyl, 4-(N′-(2-methoxyphenyl)urea)-phenyl-methyl, 4-(N′-(2-methyl-3-pyridyl)urea)-phenylmethyl, 4-(N′-(2-nitrophenyl)urea)-phenylmethyl, 4-(N′-(2-pyridyl)urea)phenylmethyl, 4-N′-(2-t-butlphenyl)-urea)phenylmethyl, 4-(N′-(2-thiazolyl)urea)-phenyl-methyl, 4-(N′-(3-chlorophenyl)urea)-phenylmethyl, 4-(N′-(3-methoxyphenyl)urea)-phenylmethyl, 4-(N′(3-pyridyl)urea)phenylmethyl, 4-(N′-(4-pyridyl)urea)-phenylmethyl, 4-(N′-(3-methylphenyl)urea)-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4-(N′-benzylurea)phenylmethyl, 4-(N′-cyclohexylurea)-phenylmethyl, 4-(N′-ethylurea)phenylmethyl, 4-(N′-isopropylurea)-phenylmethyl, 4-(N′-methylurea)-phenylmethyl, 4-(N′-p-toluylurea)phenylmethyl, 4-(N′-phenylurea)phenyl, 4-(N′phenylurea)phenylamino, 4-(N′-phenylurea)phenyl-methyl, 4(N′-t-butylurea)-phenylmethyl, 4-(phenylaminocarbonylamino-methyl)-phenyl, 4-(phenylsulfonamido)phenylmethyl, 4-(t-butoxycarbonyl-amino)-phenylmethyl, 4-acetamidophenylmethyl, 4-aminophenylamino, 4-aminophenylmethyl, 4-benzamidophenylmethyl, 4-chlorophenylmethyl, 4-hydroxy-3-nitrophenylmethyl, 4-hydroxyphenylmethyl, 4-methoxyphenylmethyl, 4-nitrophenylamino, 4- nitrophenylmethyl, 4-phenacetamidophenylmethyl, 4phenylphenylmethyl, 4-pyridylmethyl, 4-trifluoromethylphenylmethyl, 4-[2-(N′-methylurea)-benzamido]-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4(N′-phenyl-N′-methylguanidino)-phenylmethyl, 5-(N′phenylurea)pentyl, 5-(N′-t-butylurea)pentyl, 1,2,2-dimethylpropyl, 2,2-diphenylmethyl, 2,3-benzocyclobutyl, 3,4-dihydroxyphenylmethyl, 3,5-dimethoxy-4-hydroxyphenylmethyl, 4-(1-indolecarboxylamino)-phenylmethyl, 6-methoxy-5-(N′-(2-methylphenyl)urea)-2-pyridylmethyl, 4(1,3-benzoxazol-2-ylamino)-phenylmethyl, and 4-(1,3-imidazol-2-yl-amino)-phenylmethyl. 
     
     
       9. The cell adhesion inhibitory compound according to  claim 7 , wherein R 1  is selected from the group consisting of 4-hydroxyphenylmethyl, 3-methoxy-4-(N′-phenylurea)-phenylmethyl, 4-(N′-phenylurea)-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4-(N′-(2-pyridyl)urea)-phenylmethyl, 3-methoxy-4-(N′-(2-methylphenyl)urea)-phenylmethyl, 6-methoxy-5-(N′-(2-methylphenyl)urea)-2-pyridylmethyl, 4-(N′-3-methyl-2-pyridylurea)phenylmethyl, 3-methoxy-4-(N′-3-methyl-2-pyridylurea)phenylmethyl and 3-methoxy-4-(N′-2-pyridylurea)-phenylmethyl. 
     
     
       10. The cell adhesion inhibitory compound according to  claim 9 , wherein R 1  is selected from the group consisting of 4-hydroxyphenylmethyl, 3-methoxy-4-(N′-phenylurea)-phenylmethyl, 4-(N′-phenylurea)-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4-(N′-(2-pyridyl)urea)-phenylmethyl, 3-methoxy-4-(N′-(2-methylphenyl)urea)-phenylmethyl, 6-methoxy-5-(N′-(2-methylphenyl)urea)-2-pyridylmethyl. 
     
     
       11. The cell adhesion inhibitory compound according to  claim 1 , wherein Y is a carbonyl group. 
     
     
       12. The cell adhesion inhibitory compound according to  claim 1 , wherein R 2  is hydrogen, methyl, or phenacyl. 
     
     
       13. The cell adhesion inhibitory compound according to  claim 12 , wherein R 2  is hydrogen. 
     
     
       14. The cell adhesion inhibitory compound according to  claim 1 , wherein R 3  is selected from the group consisting of 2-(methylsulfonyl)-ethyl, 3-(hyrdoxy-propylthio)-methyl, 4-(methylsulfonylamino)-butyl, 4-acetylaminobutyl, aminomethyl, benzyl, butyl, hydroxymethyl, isobutyl, methyl, methylthiomethyl, phenylmethyl, propyl, 4-(benzyloxycarbonylamino)-butyl, N,N-(methylpropargyl)amino, 2-(methylthio)-ethyl, 2-(morpholino-N-carbonyl)ethyl, 2-(N-morpholino)-ethyl, 2-(N,N-dimethylamino)ethyl, 4-amino-butyl, 4-benzyloxyphenylmethyl, 2-benzylthiomethyl, t-butoxy-carbonylaminomethyl, sec-butyl, t-butyl, N,N-dimethyl-aminocarbonylmethyl, 1,1-ethano, 4-hydroxyphenylmethyl, 1-hydroxyethyl, 1-methoxyethyl, 4-methoxyphenylmethyl, benzyloxymethyl, benzylthiomethyl, carbonylmethyl, 2-methylsulfinylethyl, morpholino-N-carbonylmethyl, thiomorpholino-N-carbonyl-methyl, 2-phenylethyl, asparagine side-chain, proline side-chain and 2-thiazolylmethyl, 4-(phenylurea)butyl; 4-(methylurea)butyl; morpholinocarbonylmethylthiomethyl; morpholinoethylthiomethyl; 3-pyridylmethyl; 4-methylsulfonylaminobutyl; hydroxymethylthiomethyl; 2-methylsulfonylethyl, 4-propionylaminobutyl; 4-ethoxycarbonylaminobutyl; methoxycarbonylaminobutyl; carbomethoxymethylthiomethyl; 4-t-butylureabutyl; carboxymethylthiomethyl; dimethylamidomethylthiomethyl; acetylaminopropyl; 3-methylureapropyl; 4-biotinoylaminobutyl; 2-thienylmethyl; 3-pyridylmethyl; 4-trifluoroacetylaminobutyl; dimethylaminomethylthiomethyl; dimethylaminoethylthiomethyl; 4-(dimethylaminoacetylamino)butyl or in combination with R 2  forms a proline, azetidine or pipecolinic ring. 
     
     
       15. The cell adhesion inhibitory compound according to  claim 14 , wherein R 3  is is selected from the group consisting of 2-(methylsulfonyl)-ethyl, 3-(hyrdoxy-propylthio)-methyl, 4-(methylsulfonylamino)-butyl, 4-acetylaminobutyl, aminomethyl, benzyl, butyl, hydroxymethyl, isobutyl, methyl, methylthiomethyl, phenylmethyl, propyl, 4-(benzyloxycarbonylamino)-butyl, N,N-(methylpropargyl)amino, 2-(methylthio)-ethyl, 2-(morpholino-N-carbonyl)ethyl, 2-(N-morpholino)-ethyl, 2-(N,N-dimethylamino)ethyl, 4-amino-butyl, 4-benzyloxyphenylmethyl, 2-benzylthiomethyl, t-butoxy-carbonylaminomethyl, sec-butyl, t-butyl, N,N-dimethyl-aminocarbonylmethyl, 1,1-ethano, 4-hydroxyphenylmethyl, 1-hydroxyethyl, 1-methoxyethyl, 4-methoxyphenylmethyl, benzyloxymethyl, benzylthiomethyl, carbonylmethyl, 2-methylsulfinylethyl, morpholino-N-carbonylmethyl, thiomorpholino-N-carbonyl-methyl, 2-phenylethyl, asparagine side-chain, proline side-chain and 2-thiazolylmethyl. 
     
     
       16. The cell adhesion inhibitory compound according to  claim 14 , wherein R 3  is selected from the group consisting of isobutyl, 2-(methylthio)-ethyl, 3-(hydroxypropylthio)-methyl, 2-(methylsulfonyl)-ethyl, 4-acetylamino-butyl, 4-(methylsulfonylamino)-butyl, and 4-(ethoxycarbonylamino)butyl. 
     
     
       17. The cell adhesion inhibitory compound according to  claim 16 , wherein R 3  is is selected from the group consisting of isobutyl, 2-(methylthio)-ethyl, 3-(hydroxypropylthio)-methyl, 2-(methylsulfonyl)-ethyl, 4-acetylamino-butyl, and 4-(methylsulfonylamino)-butyl. 
     
     
       18. The cell adhesion inhibitory compound according to  claim 1 , wherein R 4  is selected from is selected from the group consisting of 4-carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, 3-pyridyl, 4-phenoxyphenyl; 4-ethoxyphenyl; 4-nitrophenyl; 4-acetylaminophenyl; 4-methylureaphenyl; 2-fluorophenyl; naphthyl; 3-fluorophenyl; 3-nitrophenyl; hydrogen; 2-nitrophenyl; 4-cyanophenyl; 3-methoxyphenyl; 4-methylsulfonylamino; 3-cyanophenyl; 4-propionylamino; 4-aminophenyl; 3-aminophenyl; 4-trifluoromethoxyphenyl; 4-methylphenyl; 4-amino-3-nitrophenyl; 4-hydroxy-3-methoxyphenyl; 4-hexyloxyphenyl; 4-methylthiophenyl; 3-furanyl; 4-dimethylaminophenyl; 3-hydroxy-4-nitrophenyl; n-pentyl; carboxymethyl; 2-carboxyethyl; ethynyl; 2-thienyl; 2-propenyl; 2-propynyl; methyl; and propyl. 
     
     
       19. The cell adhesion inhibitory compound according to  claim 18 , wherein R 4  is selected from is selected from the group consisting of 4-carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, and 3-pyridyl. 
     
     
       20. The cell adhesion inhibitory compound according to  claim 18 , wherein R 4  is selected from the group consisting 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-fluorophenyl, 4-carboxyphenyl, 4-carbomethoxyphenyl, phenylethyl, phenylmethyl, allyl, ethynyl, and 3,4-methylenedioxyphenyl. 
     
     
       21. The cell adhesion inhibitory compound according to  claim 20 , wherein R 4  is selected from the group consisting 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-fluorophenyl, 4-carboxyphenyl, 4-carbomethoxyphenyl, phenylethyl, and phenylmethyl. 
     
     
       22. The cell adhesion inhibitory compound according to  claim 1 , wherein Y is CO or SO 2 . 
     
     
       23. The cell adhesion inhibitory compound according to  claim 22 , wherein Y is CO. 
     
     
       24. The cell adhesion inhibitory compound according to  claim 1 , wherein n is 1. 
     
     
       25. A pharmaceutical composition comprising a compound according to  claim 1  in an amount effective for prevention, inhibition or suppression of cell adhesion and a pharmaceutically acceptable carrier. 
     
     
       26. The pharmaceutical composition according to  claim 25 , further comprising an agent selected from the group consisting of corticosteroids, bronchodilators, antiasthmatics, antiinflammatories, antirheumatics, immunosuppressants, antimetabolites, immunonodulators, antipsoriatics and antidiabetics. 
     
     
       27. A method of preventing, inhibiting or suppressing cell adhesion in a mammal comprising the step of administering to said mammal the pharmaceutical composition according to  claim 25 . 
     
     
       28. The method according to  claim 27 , wherein said method is used for preventing, inhibiting or suppressing cell adhesion-associated inflammation. 
     
     
       29. The method according to  claim 28 , wherein said method is used for preventing, inhibiting or suppressing a cell adhesion-associated immune or autoimmune response. 
     
     
       30. The method according to  claim 27 , wherein said method is used to treat or prevent a disease selected from the group consisting of asthma, arthritis, psoriasis, transplantation rejection, multiple sclerosis, diabetes and inflammatory bowel disease. 
     
     
       31. The cell adhesion inhibitory compound according to  claim 2 , selected from the group consisting of: 
       BIO-1006 b-alanine, N-(4-hydroxyphenyl)acetyl-L-leucyl-3 (1,3-benzodioxol-5-yl)-, (S));  
       BIO-1056 b-Alanine, N-[[4-[[(phenylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L-leucyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1179 b-Alanine, N-[[4-[[2-ethylphenylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3(1,3 benzodioxol-5-yl)-, (S),  
       BIO-1194 b-Alanine, N-[[4-[[(2-pyridylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(4methoxyphenyl)-, (S),  
       BIO-1218 b-Alanine, N-[[4-[[(2-pyridylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(3,4dimethoxyphenyl)-, (S),  
       BIO-1221 b-Alanine, N-[[4-[[(2-methylphenylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L-leucyl-3 (1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1245 b-Alanine, N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-methioninesulfonyl-3 (1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1246 b-Alanine, N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-(1 hydroxypropyl)cysteinyl-3-)1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1270 b-Alanine, N6-acetyl-N2-[[4-[[[2-methylphenyl)amino]carbonyl]amino]phenyl]acetyl]-L-lysyl-3 (1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1282 b-Alanine, N-[[4-[[)2-methylphenylamino)carbonyl]amino](3-pyridyl)]acetyl]-L-leucinyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1294 b-Alanine, N6-(methanesulfonyl)-N2-[[4-[[[2-methylphenyl)amino]carbonyl]amino]phenyl]acetyl]L-lysyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1336 b-Alanine, N-[[4-[[(2-methylphenylamino)carbonyl]amino](3-methoxy-2-pyridyl)]acetyl]-L leucinyl-3(1,3-benzodioxol-5-yl)-, (S)—.  
     
     
       32. The cell adhesion inhibitory compound according to  claim 1 , selected from the group consisting of: 
       BIO-1218 b-Alanine, N-[[4-[[(2-pyridylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-2-(3,4 dimethoxyphenyl)-, (S)—,  
       BIO-1272 b-Alanine, N6-(methoxycarbonyl)-N2-[[4-[[[2 methylphenyl)amino]carbonyl]amino]phenyl]acetyl]-L-lysyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1311 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(3,4 dimethoxyphenyl)-, (S),  
       BIO-1319 b-Alanine, N-[[4-[[1-dihydroindole)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol 5-yl)-, (S)—,  
       BIO-1345 b-Alanine, N2-[[4-[[[2-methylphenyl)amino]carbonyl]amino]phenyl]acetyl]-L-[(N,N dimethylaminoethyl)-(cysteinyl)]-3-(1,3-benzodioxol-5-yl)-, (S),  
       BIO-1347 b-Alanine, N-[[4-[[2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(3,4 dimethoxyphenyl)-, (S)—,  
       BIO-1358 b-Alanine, N-[[4-[[(phenylamino)thiocarbonyl]amino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol 5-yl)-, (S)—,  
       BIO-1390 b-Alanine, N-[[4-[[(1,3-benzimidazolecarbonyl]amino]phenyl]acetyl]-L-leucyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1393 b-Alanine, N-[[4-[[-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1396 b-Alanine, N-[[4-[[(1,3-benzoxazolecarbonyl]amino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol 5-yl)-, (S)—,  
       BIO-1429 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1444 b-Alanine, N-[[4-[[(2-acetoxyphenylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1474 b-Alanine, N-[[4-[[(2-pyrolocarbonyl]amino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1475 b-Alanine, N-[[4-[[(allylcarbonly]amino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1648 b-Alanine, N-[[4-[[1H-indol-2-yl-carbonylamino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1655 b-Alanine, N-[[4-[[1H-indol-3-yl-carbonylamino]phenyl]acetyl]-L-leucyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1721 b-Alanine, N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(4 methylmorpholinyl)-, (S)—,  
       BIO-1725 b-Alanine, N-[[4-[[(phenylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L-methionyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1728 b-Alanine, N-[[4-[[-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L-methionyl-3 (3,4-dimethoxyphenyl)-, (S)—,  
       BIO-1729 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L leucyl-3-(3,4-dimethoxyphenyl)-, (S)—,  
       BIO-1730 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl][amino](3-methoxyphenyl)]acetyl]-L methionyl-3-(3,4-dimethoxyphenyl)-, (S)—,  
       BIO-1731 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L methionyl-3-(1,3-benzodioxol-5-y)-, (S)—,  
       BIO-1732 b-Alanine, N-[[4-[[5[methyl-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(3,4 dimethoxyphenyl)-, (S)—.  
     
     
       33. The cell adhesion inhibitory compound according to  claim 1 , selected from the group consisting of: 
       BIO-1218 b-Alanine,N-[[4-[[(2-pyridylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(3,4 dimethoxyphenyl)-, (S)—,  
       BIO-1272 b-Alanine,N6-(methoxycarbonyl)-N2-[[4-[[[2 methylphenyl)amino]carbonyl]amino]carbonyl]amino]phenyl]acetyl]-L-lysyl-3-(1,3-benzodioxol-5-yl)-, (S)—,  
       BIO-1311 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-leucyl-3-(3,4 dimethoxyphenyl)-, (S)—,  
       BIO-1347 b-Alanine, N-[[4[[-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(3,4 dimethoxyphenyl)-, (S)—,  
       BIO-1393 b-Alanine, N-[[4-[[-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1429 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(1,3 benzodioxol-5-y)-, (S)—,  
       BIO-1725 b-Alanine, N-[[4-[[(phenylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L-methionyl-3-(1,3 benzodioxol-5-yl)-, (S)—,  
       BIO-1728 b-Alanine, N-[[4-[[-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L-methionyl-3-(3,4-dimethoxyphenyl)-, (S)—,  
       BIO-1729 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L leucyl-3-(3,4-dimethoxyphenyl)-, (S)—,  
       BIO-1730 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L methionyl-3-(3,4-dimethoxyphenyl)-, (S)—,  
       BIO-1731 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino](3-methoxyphenyl)]acetyl]-L methionyl-3-(1,3-benzodioxol-5-y)-, (S)—,  
       BIO-1732 b-Alanine, N-[[4-[[5-methyl-2-pyridinylamino)carbonyl]amino]phenyl]acetyl]-L-methionyl-3-(3,4 dimethoxyphenyl)-, (S).  
     
     
       34. A cell adhesion inhibitory compound selected from a compound of the formula (I):                    
       and pharmaceutically acceptable derivatives of (I), wherein: 
       X is selected from the group consisting of —CO 2 H, —PO −   3 H, —SO 2 R 5 , —SO 3 H, and —OPO −   3 H; wherein R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aryl-substituted alkyl, and aryl-substituted alkenyl or alkynyl;  
       Y is selected from the group consisting of —CO—, —SO 2 — and —PO 2 —;  
       R 1  is (N′-Ar-urea)-substituted arylalkyl, wherein the urea is substituted at the para position of an arylalkyl;  
       R 2  is selected from the group consisting of hydrogen, aryl, alkyl, alkenyl or alkynyl, cycloalkyl, cycloalkenyl, aryl-substituted alkyl and, wherein R 2  and R 3  may be taken together with the atoms to which they are attached, to form a heterocycle;  
       R 3  is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl-substituted alkenyl or alkynyl, hydroxy-substituted alkyl, alkoxy-substituted alkyl, aryloxy-substituted alkyl, amino-substituted alkyl, (aryl-substituted alkyloxycarbonylamino)-substituted alkyl, thiol-substituted alkyl, alkylsulfonyl-substituted alkyl, (hydroxy-substituted alkylthio)-substituted alkyl, thioalkoxy-substituted alkyl, acylamino-substituted alkyl, alkylsulfonylamino-substituted alkyl, arylsulfonylamino-substituted alkyl, morpholino-alkyl, thiomorpholino-alkyl, morpholino carbonyl-substituted alkyl, thiomorpholinocarbonyl-substituted alkyl, N-(alkyl, alkenyl or alkynyl)- or N,N-(dialkyl, dialkenyl, dialkynyl)- or N,N-(alkyl, alkenyl)-aminocarbonyl-substituted alkyl, carboxyl-substituted alkyl, dialkylamino-substituted acylaminoalkyl and amino acid side chains selected from arginine, asparagine, glutamine, S-methyl cysteine, methionine and corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoleucine, allo-isoleucine, tert-leucine, norleucine, phenylalanine, tyrosine, tryptophan, proline, alanine, ornithine, histidine, glutamine, valine, threonine, serine, beta-cyanoalanine, and allothreonine; and wherein R 2  and R 3  may be taken together with the atoms to which they are attached, to form a heterocycle;  
       R 4  is selected from the group consisting of aryl, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl and aryl-substituted alkyl, hydrogen, heterocyclyl, heterocyclylcarbonyl, amido, mono- or dialkylaminocarbonyl, mono- or diarylaminocarbonyl, alkylarylaminocarbonyl, diarylaminocarbonyl, mono- or diacylaminocarbonyl, aromatic acyl, alkyl optionally substituted by substituents selected from the group consisting of amino, carboxy, hydroxy, mercapto, mono- or dialkylamino, mono- or diarylamino, alkylarylamino, diarylamino, mono- or diacylamino, alkoxy, alkenyloxy, aryloxy, thioalkoxy, thioalkenoxy, thioalkynoxy, thioaryloxy and heterocyclyl;  
       n is 0, 1, or 2; and  
       at least one of R 2 -R 5  includes a heterocyclic group.  
     
     
       35. The cell adhesion inhibitory compound according to  claim 34 , wherein R1 is a (N′-Ar-urea), wherein the urea is substituted at the para position of phenylmethyl. 
     
     
       36. The cell adhesion inhibitory compound according to  claim 34 , wherein R1 is selected from the group consisting of 3-methoxy-4-(N-phenylurea)-phenylmethyl, 4-(N′-phenylurea)-phenylmethyl, 4-(N′-(2-methylphenyl)urea)-phenylmethyl, 4-(N′-(2-pyridyl)urea)-phenylmethyl, 3-methoxy-4-(N′-(2methylphenyl)urea)-phenylmethyl, 6-methoxy-5-(N′-(2methylphenyl)urea)-2-pyridylmethyl, 4-(N′-3-methyl-2-pyridylurea)phenylmethyl, 3-methoxy-4-(N′-3-methyl-2-pyridylurea)phenylmethyl and 3-methoxy-4-(N′-2-pyridylurea)-phenylmethyl. 
     
     
       37. The cell adhesion inhibitory compound according to  claim 34 , wherein R3 is selected from the group consisting of 2-(methylsulfonyl)-ethyl, 3-(hydroxy-propylthio)-methyl, 4-(methylsulfonylamino)-butyl, 4-acetylaminobutyl, aminomethyl, benzyl, butyl, hydroxymethyl, isobutyl, methyl, methylthiomethyl, phenylmethyl, propyl, 4-(benzloxycarbonylamino)-butyl, N,N-(methylpropargyl)amino, 2-(methylthio)-ethyl, 2-(morpholino-N-carbonyl)ethyl, 2-(N-morpholino)-ethyl, 2-(N,N-dimethylamino)ethyl, 4-amino-butyl, 4-benzyloxyphenylmethyl, 2-benzylthiomethyl, t-butoxy-carbonylaminomethyl, sec-butyl, t-butyl, N,N-dimethylaminocarbonylmethyl, 1,1-ethano, 4-hydroxyphenylmethyl, 1-hydroxyethyl, 1-methoxyethyl, 4-methoxyphenylmethyl, benzyloxymethyl, benzylthiomethyl, carbonylmethyl, 2-methylsulfinylethyl, morpholino-N-carbonylmethyl, thiomorpholino-N-carbonyl-methyl, 2-phenylethyl, asparagine side-chain, proline side-chain and 2-thiazolylmethyl, 4-(phenylurea)butyl; 4-(methylurea)butyl; morpholinocarbonylmethylthiomethyl; morpholinoethylthiomethyl; 3-pyridylmethyl; 4-methylsulfonylaminobutyl; hydroxymethylthiomethyl; 2-methylsulfonylethyl, 4-propionylaminobutyl; 4-ethoxycarbonylaminobutyl; methoxycarbonylaminobutyl; carbomethoxymethylthiomethyl; 4-t-butylureabutyl; carboxymethylthiomethyl; dimethylamidomethylthiomethyl; acetylaminopropyl; 3-methylureapropyl; 4-biotinoylaminobutyl; 2-thienylmethyl; 3-pyridylmethyl; 4-trifluoroacetylaminobutyl; dimethylaminomethylthiomethyl; dimethylaminoethylthiomethyl; 4-(dimethylaminoacetylamino)butyl or in combination with R2 forms a proline, azetidine or pipecolinic ring. 
     
     
       38. The cell adhesion inhibitory compound according to  claim 37 , wherein R3 is selected from the group consisting of 2-(methylsulfonyl)-ethyl, 3-(hydroxy-propylthio)-methyl, 4-(methylsulfonylamino)-butyl, 4-acetylaminobutyl, aminomethyl, benzyl, butyl, hydroxymethyl, isobutyl, methyl, methylthiomethyl, phenylmethyl, propyl, 4-(benzyloxycarbonylamino)-butyl, N,N-(methylpropargyl)amino, 2-(methylthio)-ethyl, 2-(morpholino)-ethyl, 2-(N,N-dimethylamino)ethyl, 4-amino-butyl, 4-benzyloxyphenylmethyl, 2-benzylthiomethyl, t-butoxy-carbonylaminomethyl, sec-butyl, t-butyl, N,N-dimethylaminocarbonylmethyl, 1,1-ethano, 4-hydroxyphenylmethyl, 1-hydroxyethyl, 1-methoxyethyl, 4-methoxyphenylmethyl, benzloxymethyl, benzylthiomethyl, carbonylmethyl, 2-methylsulfinylethyl, morpholino-N-carbonylmethyl, thiomorpholino-N-carbonyl-methyl, 2-phenylethyl, asparagine side-chain, proline side-chain and 2-thiazolylmethyl. 
     
     
       39. The cell adhesion inhibitory compound according to  claim 37 , wherein R3 is selected from the group consisting of isobutyl, 2-(methylthio)-ethyl, 3-(hydroxypropylthio)-methyl, 2-(methylsulfonyl)-ethyl, 4-acetylamino-butyl, 4-(methylsulfonylaamino)-butyl, and 4-(ethoxycarbonylamino)butyl. 
     
     
       40. The cell adhesion inhibitory compound according to  claim 39 , wherein R3 is selected from the group consisting of isobutyl, 2-(methylthio)-ethyl, 3-(hydroxypropylthio)-methyl, 2-(methylsulfonyl)-ethyl, 4-acetylamino-butyl, and 4-(methylsulfonylamino)-butyl. 
     
     
       41. The cell adhesion inhibitory compound according to  claim 34 , wherein R4 is selected from the group consisting of 4-carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, 3-pyridyl, 4-phenoxyphenyl; 4-ethoxyphenyl; 4-nitrophenyl; 4-acetylaminophenyl; 4-methylureaphenyl; 2-fluorophenyl; napthyl; 3-fluorophenyl; 3-nitrophenyl; hydrogen; 2-nitrophenyl; 4-cyanophenyl; 3-methoxyphenyl; 4-methylsulfonylamino; 3-cyanophenyl; 4-propionylamino; 4-aminophenyl; 3-aminophenyl; 4-trifluoromethoxyphenyl; 4-methylphenyl; 4-amino-3-nitrophenyl; 4-hydroxy-3-methoxyphenyl; 4-hexyloxyphenyl; 4-methylthiophenyl; 3-furanyl; 4-dimethylaminophenyl; 3-hydroxy-4-nitrophenyl; n-pentyl; carboxymethyl; 2-carboxyethyl; ethynyl; 2-thienyl; 2-propenyl; 2-propynyl; methyl and propyl. 
     
     
       42. The cell adhesion inhibitory compound according to  claim 41 , wherein R4 is selected of 4-carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, 3-pyridyl. 
     
     
       43. The cell adhesion inhibitory compound according to  claim 41 , wherein R4 is selected from the group consisting 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-fluorophenyl, 4-carboxyphenyl, 4-carbomethoxyphenyl, phenylethyl, phenylmethyl, allyl, ethynyl, and 3,4-methylenedioxyphenyl. 
     
     
       44. The cell adhesion inhibitory compound according to  claim 43 , wherein R4 is selected from the group consisting 4-methoxyphenyl, 3,4-dimethoxyphenyl, 4-fluorophenyl, 4-carboxyphenyl, 4-carbomethoxyphenyl, phenylethyl, and phenylmethyl. 
     
     
       45. The cell adhesion inhibitory compound of  claim 1 , wherein R 1  is selected from the group consisting of alkenyl, alkynyl, cycloalkyl, aryl-fused cycloalkyl, cycloalkenyl, aryl, aralkyl, aryl-substituted alkenyl or alkynyl, cycloalkenyl-substituted alkyl, alkylamino, alkenylamino or alkynylamino, aryl-substituted alkylamino, aryl-substituted alkenylamino or alkenylamino, N-alkylurea-substituted alkyl, N-arylurea-substituted alkyl, and aminocarbonyl-substituted alkyl. 
     
     
       46. The cell adhesion inhibitory compound of  claim 1 , wherein Y is CO, R 1  is (N-Ar′-urea)-para-substituted aralkyl group; R 2  is H; R 3  is selected from the group consisting of isobutyl, 2-(methylthio)-ethyl, 3-(hydroxypropylthio)-methyl, 2-(methylsulfonyl)-ethyl, 4-acetylamino-butyl, 4-(methylsulfonylamino)-butyl, and 4-(ethoxycarbonylamino)butyl; and R 4  is selected from the group consisting of 4 carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, and 3-pyridyl. 
     
     
       47. The cell adhesion inhibitory compound of  claim 1 , wherein Y is SO 2 ; R 2  is H; R 3  is selected from the group consisting of isobutyl, 2-(methylthio)-ethyl, 3-(hydroxypropylthio)-methyl, 2-(methylsulfonyl)-ethyl, 4-acetylamino-butyl, 4-(methylsulfonylamino)-butyl, and 4-(ethoxycarbonylamino)butyl; and R 4  is selected from the group consisting of 4 carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3, 4-difluorophenyl, 3, 4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, and 3-pyridyl. 
     
     
       48. The cell adhesion inhibitory compound of  claim 1 , wherein R 2  is selected from the group consisting of aryl, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and aryl-substituted alkyl. 
     
     
       49. The cell adhesion inhibitory compound of  claim 1 , wherein R 2  and R 3 , together with the atoms to which they are attached, form a heterocycle. 
     
     
       50. The cell adhesion inhibitory compound of  claim 49 , wherein R 2  and R 3 , together with the atoms to which they are attached, form a monocyclic or bicyclic heterocyclic ring. 
     
     
       51. The cell adhesion inhibitory compound of  claim 50 , wherein the bicyclic heterocyclic ring contains a heterocyclic ring and a cycloalkyl or an aryl. 
     
     
       52. The cell adhesion inhibitory compound of  claim 49 , wherein the heterocycle is optionally substituted with hydroxyl, amino, alkyl, Ar′-substituted carbonylamino, Ar′-substituted amino, alkylcarbonylamino, Ar′-substituted alkylcarbonylamino, heterocyclylamino, benzofused-heterocyclylcarbonylamino, Ar′,Ar′-disubstituted acylamino, heterocyclylcarbonylamino, heterocyclylalkylamino, cycloalkyl-substituted amino, or Ar′-substituted arylamino. 
     
     
       53. The cell adhesion inhibitory compound of  claim 1 , wherein Y is CO, R 1  is (N-Ar′-urea)-para-substituted aralkyl group; R 2  and R 3 , together with the atoms to which they are attached, form a heterocycle; and R 4  is selected from is selected from the group consisting of 4 carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, and 3-pyridyl. 
     
     
       54. The cell adhesion inhibitory compound of  claim 53 , wherein R 2  and R 3 , together with the atoms to which they are attached, form a monocyclic or bicyclic heterocyclic ring; the heterocyclic ring being optionally substituted with hydroxyl, amino, alkyl, Ar′-substituted carbonylamino, Ar′-substituted amino, alkylcarbonylamino, Ar′-substituted alkylcarbonylamino, heterocyclylamino, benzofused-heterocyclylcarbonylamino, Ar′,Ar′-disubstituted acylamino, heterocyclylcarbonylamino, heterocyclylalkylamino, cycloalkyl-substituted amino, or Ar′-substituted arylamino. 
     
     
       55. The cell adhesion inhibitory compound of  claim 1 , wherein Y is SO 2 ; R 2  and R 3 , together with the atoms to which they are attached, form a heterocycle; and R 4  is selected from is selected from the group consisting of 4 carbomethoxy-phenyl, 4-carboxyphenyl, 4-fluorophenyl, 4-methoxy-phenyl, benzyl, methyl, phenyl, phenylmethyl, phenylethyl, 4-chlorophenyl, 3,4-difluorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 3 -methoxyphenyl, 4-methoxyphenyl, 2-nitrophenyl, and 3-pyridyl. 
     
     
       56. The cell adhesion inhibitory compound of  claim 55 , wherein R 2  and R 3 , together with the atoms to which they are attached, form a monocyclic or bicyclic heterocyclic ring; the heterocyclic ring being optionally substituted with hydroxyl, amino, alkyl, Ar′-substituted carbonylamino, Ar′-substituted amino, alkylcarbonylamino, Ar′-substituted alkylcarbonylamino, heterocyclylamino, benzofused-heterocyclylcarbonylamino, Ar′,Ar′-disubstituted acylamino, heterocyclylcarbonylamino, heterocyclylalkylamino, cycloalkyl-substituted amino, or Ar′-substituted arylamino.